Progesterone (P4) is essential to maintenance of primate gestation and cortisol (F) to fetal lung maturation and possibly the onset of labor in primates. The regulatory factor(s) involved in production of these steroids, however, are unknown. Preliminary studies by the applicants in baboons implicate estrogen in this regard and the fetus appears important to maternal P4 production. The proposed consortium study would determine in pregnant baboons: (a) the role, site and mechanism of action of estrogen and influence of the fetus upon placental and ovarian P4 production and (b) the influence of estrogen, the fetus and advancing gestation upon trans- and intra-uterine F and cortisone(E) interconversion and intrauterine metabolism of P4. Pregnant baboons will be administered the antiestrogen MER-25 daily between 130 days gestation and term (184 days, spontaneous delivery) or near term (175 days, cesarean section) in order to block the action of endogenous estrogen. In other baboons the fetus will be surgically removed at midgestation. Serum P4, 17-hydroxyprogesterone, estrone, and estradiol concentrations will be measured by radioimmunoassay on blood collected at 1-4 day intervals to determine the influence of antiestrogen administration and fetectomy upon production of these steroids. The conversion of maternally administered (3H) pregnenolone (P5) to (3H)P4 will be assessed to elucidate the mechanism of action. In vitro production of P4 by cells of the corpus luteum and serum P4 levels in the uteroovarian vein will be assessed to determine site (placental or luteal) of action of estrogen and the fetus upon P4 production. A constant IV infusion of (3H)F/(14C)E and (3H)P4/(14C) 20 alpha-hydroxyprogesterone (20 alpha-OHP4) will be administered maternally at mid and late gestation and in antiestrogen-treated and fetectomized baboons. (3H)/(14C)F, E and 20 alpha-OHP4 will be purified from saphenous uterine and umbilical vein serum and endometrial tissue to determine the role of estrogen, the fetus and effect of advancing gestation upon uterine extraction of F and E, trans- and intra-uterine interconversion of F and E and intrauterine metabolism of P4. Baboon neonates delivered from untreated and MER-25-treated mothers will be infused with (3H)P5/(14C)P4 and (3H)F/(14C)E, respectively, to determine the contribution of p (Text Truncated - Exceeds Capacity)